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Vedovati M.C.,University of Perugia | Becattini C.,University of Perugia | Rondelli F.,University of Perugia | Boncompagni M.,General Surgery | And 7 more authors.
Annals of Surgery | Year: 2014

OBJECTIVE:: To compare the efficacy and safety of antithrombotic prophylaxis given for 1 week or 4 weeks in patients undergoing laparoscopic surgery for colorectal cancer. BACKGROUND:: Extending antithrombotic prophylaxis beyond 1 week reduces the incidence of venous thromboembolism (VTE) after open abdominal surgery for cancer. METHODS:: In consecutive patients who underwent laparoscopic surgery for colorectal cancer, complete compression ultrasonography of the lower limbs was performed after 8 ± 2 days of antithrombotic prophylaxis. Patients with no evidence of VTE were randomized to short (heparin withdrawal) or to extended (heparin continued for 3 additional weeks) prophylaxis. Complete compression ultrasonography was repeated at day 28 ± 2 after surgery by investigators blinded to treatment allocation. The primary outcome of the study was the composite of symptomatic and ultrasonography-detected VTE at day 28 ± 2 after surgery. RESULTS:: Overall, 301 patients were evaluated for inclusion in the study and 225 were randomized. VTE occurred in 11 of 113 patients randomized to short (9.7%) and in none of the 112 patients randomized to extended heparin prophylaxis (P = 0.001). The incidence of VTE at 3 months was 9.7% and 0.9% in patients randomized to short or to extended heparin prophylaxis, respectively (relative risk reduction: 91%, 95% confidence interval: 30%-99%; P = 0.005). The rate of bleeding was similar in the 2 treatment groups. Two patients died during the study period, 1 in each treatment group. CONCLUSIONS:: After laparoscopic surgery for colorectal cancer, extended antithrombotic prophylaxis is safe and reduces the risk for VTE as compared with 1-week prophylaxis (NCT01589146). © 2013 by Lippincott Williams & Wilkins.

Bassi N.,University of Padua | Luisetto R.,Oncological and Gastroenterological science | Ghirardello A.,University of Padua | Gatto M.,University of Padua | And 5 more authors.
Lupus | Year: 2015

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice.Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice.We implanted pellets releasing 17-β-estradiol (18.8-μg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200-μl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death.BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q (R2-=-0.6962, p-<-0.0001) or anti-dsDNA (R2-=-0.5953, p-<-0.0001), and between anti-C1q and anti-dsDNA autoantibodies (R2-=-0.5615, p-<-0.0001) were found. Proteinuria-free and global survival rates were significantly lower in group 1 than in controls. Histological analyses showed more severe abnormalities in group 1 mice.Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Agostini M.,Oncological and Gastroenterological science | Agostini M.,Methodist Hospital Research Institute | Enzo M.V.,Oncological and Gastroenterological science | Bedin C.,Oncological and Gastroenterological science | And 9 more authors.
Cancer Biomarkers | Year: 2012

Purpose: We undertook the current study with untreated breast cancer to (1) role the variations in the plasma levels of cfDNA and the size distribution in early stage, (2) determine the frequency in plasma of methylation of three candidate genes, RASSF1A, MAL, and SFRP1, and (3) to determine whether detection of cfDNA variations and methylation changes in plasma might have specific clinical utility. Methods and materials: Thirty-nine patients woman patients (median age 64 years; range, 36-90 years) who underwent surgery for primary BR and 49 healthy females' subjects (control group without any breast lesion) were evaluated. The cfDNA levels were analyzed using quantitative real-time polymerase chain reaction of β-globin. Based on the ALU repeats, the cfDNA was considered as either total (fragments of 115 bp, ALU115) or tumoral (fragments of 247 bp, ALU247). The association between the levels of the ALU247, ALU115 repeat, and ALU 247/115and the pathologic tumor characteristics was analyzed. Used methylight qPCR method, cfDNA from plasma samples of healthy donors and patients with breast cancer were evaluated for the diagnotic value of the methylation status of three genes (RASSF1A, MAL, SFRP1) frequently methylated in breast cancer. Results: The baseline levels of cfDNA were significantly higher in the patients with cancer, and the level of ALU247 was the most accurate circulating cfDNA marker in discriminating the cancer from non-cancer subjects. A high statistical significance was found by considering the T stage and patients with regional LN metastasis positive cancers showed significantly higher cfDNA level of ALU247. Moreover, patients with methylation of at least one of the gene under investigate showed a higher quantity of cfDNA ALU115 (p< 0.0001) and ALU247 level (p< 0.0001). Conclusions: We observed that necrosis could be a potential source of circulating tumour-specific cfDNA ALU247; and that cfDNA ALU247 and methylated cfDNA (RASSF1A, MAL and SFRP1) are both a phenotypic feature of tumour biology. ©2012-IOS Press and the authors. All rights reserved.

Savarino E.,Oncological and Gastroenterological science | Savarino V.,University of Genoa | Fox M.,NIHR Biomedical Research Unit | Di Leo G.,Servizio di Radiologia | And 10 more authors.
European Radiology | Year: 2015

Objectives: To assess prospectively the agreement of orocaecal transit time (OCTT) measurements by lactulose hydrogen breath test (LHBT) and magnetic resonance imaging (MRI) in healthy subjects. Methods: Volunteers underwent abdominal 1.5-T MRI using axial and coronal single-shot fast-spin-echo T2-weighted sequences, having fasted and after lactulose ingestion (10 g/125 mL). Imaging and H2 excretion gas-chromatography were performed concurrently every 15 min up to 180 min. MR images were analyzed using semiautomatic segmentation to calculate small bowel gas volume (SBGV) and visually to detect bolus arrival in the caecum. Agreement between MRI- and LHBT-OCTT was assessed. Results: Twenty-eight subjects (17 men/11 women; mean age ± standard deviation 30 ± 8 years) were evaluated. Two H2 non-producers on LHBT were excluded. OCTT measured by MRI and LHBT was concordant in 18/26 (69 %) subjects (excellent agreement, k = 0.924). Median SBGV was 49.0 mL (interquartile interval 44.1 – 51.6 mL). In 8/26 (31 %) subjects, MRI showed that the lactulose bolus was in the terminal ileum and not the caecum when H2E increased on LHBT. Median OCTT measured by MRI was significantly longer than OCTT measured by LHBT [135 min (120 – 150 min) vs. 127.5 min (105 – 150 min); p = 0.008]. Above baseline levels, correlation between [H2] and SBGV was significant (r = 0.964; p < 0.001). Conclusions: MRI provides valid measurements of OCTT and gas production in the small bowel. Key Points: • MRI is a valid technique to measure OCTT. • Excellent agreement between MRI and LHBT was found. • Measuring gas production using MRI may provide evidence of small bowel fermentation. © 2015, European Society of Radiology.

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